U.S. patent number 3,883,305 [Application Number 05/341,069] was granted by the patent office on 1975-05-13 for automatic chemical analysis apparatus.
This patent grant is currently assigned to Coulter Electronics, Inc.. Invention is credited to Arthur William Dunsmore, Thomas Horne, Douglas Haig Hoskins, Graham Roger Jarman.
United States Patent |
3,883,305 |
Hoskins , et al. |
May 13, 1975 |
Automatic chemical analysis apparatus
Abstract
An automatic chemical analysis apparatus having separate
closed-looped conveyors for sample and reactant containers. At a
fixed location, sample portions from a given sample are transferred
to a serial sequence of reactant containers. Colourimetric testing
is arranged such that all of the reactant products of the given
sample are tested simultaneously. Sample and reactant products
identification are obtained at the time the reactant containers are
at the colourimeter station, at which time the sample container is
at a variably positioned identification station, the position being
dictated by the number of sample portions being tested for that
given sample.
Inventors: |
Hoskins; Douglas Haig (St.
Albans, EN), Horne; Thomas (Woburn Bletchley,
EN), Jarman; Graham Roger (Dunstable, EN),
Dunsmore; Arthur William (Dunstable, EN) |
Assignee: |
Coulter Electronics, Inc.
(Hialeah, FL)
|
Family
ID: |
10019398 |
Appl.
No.: |
05/341,069 |
Filed: |
March 14, 1973 |
Foreign Application Priority Data
|
|
|
|
|
Mar 21, 1972 [GB] |
|
|
13241/72 |
|
Current U.S.
Class: |
422/65; 422/534;
422/547; 422/67; 422/72; 141/130; 422/69; 422/109 |
Current CPC
Class: |
G01N
35/021 (20130101); G01N 35/02 (20130101) |
Current International
Class: |
G01N
35/02 (20060101); G01n 033/16 (); G01n
001/18 () |
Field of
Search: |
;23/230,259,253
;73/425.4P,425.4R ;141/130 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Serwin; R. E.
Attorney, Agent or Firm: Silverman & Cass, Ltd.
Claims
What is desired to be secured by United States Letters Patent
is:
1. An apparatus for automatic chemical analysis comprising: a first
sequentially advanceable conveyor for carrying containers holding
samples to be tested; a second sequentially advanceable conveyor
for carrying reaction tubes in which chemical reactions can be
caused to occur; said conveyors defining paths which lie one within
the other; first and second transfer stations fixedly positioned
along the path of said first and second conveyors, respectively;
transfer structure positioned adjacent said first and second
stations for sequentially transferring sample portions from each
container, when it is at said first station, to a predetermined
plurality of the reaction tubes as they are moved past said second
station; apparatus capable of adding different reagents to each of
said plurality of reaction tubes; a programmed drive arrangement
for advancing said first conveyor to present a next sample
container to said first station in conjunction with advancing said
second conveyor to present a next plurality of reaction tubes
sequentially to said second station for sample transferring; and
testing equipment for testing the reaction products of each of said
plurality of reaction tubes.
2. Apparatus according to claim 1 in which at least one of said
conveyors and preferably each said conveyor operates in a
horizontally closed loop for carrying its respective containers and
tubes in a closed loop.
3. Apparatus according to claim 2 in which said testing equipment
includes a testing station which sequentially receives all of said
plurality of reaction tubes as a group for substantially
simultaneous individual testing of the contents thereof.
4. Apparatus according to claim 1 in which said transfer structure
includes a pipette which comprises a pair of electrically
conductive members, one of said pair being a tube through which
sample can be drawn from said containers, said members being
electrically insulated from each other and mechanically linked to
one another so as to be moved as a unit relative to the level of
the sample within a sample container and be placed in physical and
electrical contact with the sample, said tube member having a lower
end which extends a determinable distance beyond that of said other
member into the sample, and an electrical conductor connected to
each said member; whereby, when said pipette is immersed into the
sample said determinable distance, a responsive electric signal can
be derived from said conductors.
5. Apparatus according to claim 4 which further comprises an
identification station for correlation of sample and reaction
product identification, such that the test results of each reaction
product is identified with respect to its originating sample, said
identification station being moveably positionable along the path
of and adjacent said first conveyor subsequent to said first
transfer station, the position of said identification station being
predetermined by the number of reaction tubes in said plurality of
reaction tubes for a specific sample, whereby a sample container
will have reached said identification station at the same time that
all of its associated plurality of reaction tubes will have reached
said testing equipment, for simultaneous identification
purposes.
6. Apparatus according to claim 1 which further comprises an
identification station for correlation of sample and reaction
product identification, such that the test results of each reaction
product is identified with respect to its originating sample, said
identification station being moveably positionable along the path
of and adjacent said first conveyor subsequent to said first
transfer station, the position of said identification station being
predetermined by the number of reaction tubes in said plurality of
reaction tubes for a specific sample, whereby a sample container
will have reached said identification station at the same time that
all of its associated plurality of reaction tubes will have reached
said testing equipment, for simultaneous identification
purposes.
7. Apparatus according to claim 6 in which said testing equipment
is positioned adjacent said second conveyor and is relatively
moveable along the path thereof, the positioning of said testing
equipment being predetermined and based upon the number of reaction
tubes in said plurality of reaction tubes for each specific
sample.
8. Apparatus according to claim 1 in which said testing equipment
includes a testing station which sequentially receives all of said
plurality of reaction tubes as a group for substantially
simultaneous individual testing of the contents thereof.
9. Apparatus according to claim 1 which further comprises an
identification station for correlation of sample and reaction
product identification, such that the test results of each reaction
product is identified with respect to its originating sample, said
identification station being moveably positionable along the path
of and adjacent said first conveyor subsequent to said first
transfer station, the position of said identification station being
predetermined by the number of reaction tubes in said plurality of
reaction tubes for a specific sample, whereby a sample container
will have reached said identification station at the same time that
all of its associated plurality of reaction tubes will have reached
said testing equipment, for simultaneous identification
purposes.
10. Apparatus according to claim 1 in which said testing equipment
includes colourimetric testing devices arranged parallel said
second conveyor for each of said predetermined plurality of
reaction tubes.
11. Apparatus according to claim 10 in which said testing equipment
includes a light source and structure for directing the
illumination energy of said light source toward the reaction
products being tested, whilst directing the heat energy from said
light source away from said reaction products.
12. Apparatus according to claim 11 in which said energy directing
structure comprises a dichroic reflector.
13. Apparatus according to claim 12 in which said dichroic
reflector is constructed to transmit energy wavelengths exceeding
1000 nm away from the material to be tested.
14. Apparatus according to claim 1 which further comprises a third
sequentially advanceable conveyor for carrying reaction tubes;
third and fourth transfer stations fixedly positioned along the
path of said first and third conveyors, respectively; a second
transfer structure constructed and arranged for transferring at
least one sample portion from a container at said third station to
at least one reaction tube at said fourth station for subsequent
receipt of reagents and testing; and said programmed drive
arrangement coordinating the sequential advancing of said third
conveyor relative to the advancing of said first conveyor.
15. Apparatus according to claim 14 in which temperature control
structure is provided to establish a temperature difference between
the contents in the reactant tubes on said second conveyor with
respect to the contents in the reactant tubes on said third
conveyor.
16. Apparatus according to claim 15 in which at least one of said
conveyors and preferably each said conveyor operates in a
horizontally closed loop for carrying its respective containers and
tubes in a closed loop.
17. Apparatus according to claim 1 in which said transfer structure
includes a pipette and translation structure for moving said
pipette both horizontally between said fixed transfer stations and
vertically with respect to said containers and tubes at said
transfer stations.
18. Apparatus according to claim 17 in which said pipette comprises
a pair of electrically conductive members, one of said pair being a
tube through which sample can be drawn from said containers, said
members being electrically insulated from each other and
mechanically linked to one another so as to be moved as a unit
relative to the level of the sample within a sample container and
be placed in physical and electrical contact with the sample, said
tube member having a lower end which extends a determinable
distance beyond that of said other member into the sample, and an
electrical conductor connected to each said member; whereby, when
said pipette is immersed into the sample said determinable
distance, a responsive electric signal can be derived from said
conductors.
19. Apparatus according to claim 18 in which said conductive
members are adjustably linked to one another for varying said
determinable distance.
20. Apparatus according to claim 18 in which said other member also
is a tube and surrounds said sample drawing tube for most of its
length, except for said determinable distance.
21. Apparatus according to claim 1 in which said testing equipment
includes a testing station which sequentially receives all of said
plurality of reaction tubes as a group for substantially
simultaneous individual testing of the contents thereof.
22. Apparatus according to claim 21 which further comprises an
identification station for correlation of sample and reaction
product identification, such that the test results of each reaction
product is identified with respect to its originating sample, said
identification station being moveably positionable along the path
of and adjacent said first conveyor subsequent to said first
transfer station, the position of said identification station being
predetermined by the number of reaction tubes in said plurality of
reaction tubes for a specific sample, whereby a sample container
will have reached said identification station at the same time that
all of its associated plurality of reaction tubes will have reached
said testing equipment, for simultaneous identification
purposes.
23. Apparatus according to claim 21 in which said testing equipment
includes a plurality of cuvettes in fixed position, equal in number
of the maximum number in said predetermined plurality of reaction
tubes, and reaction product transfer structure coupled to said
cuvettes for effecting transfer to and from said cuvettes of the
reaction products of a said plurality of reaction tubes,
substantially simultaneously.
24. Apparatus according to claim 23 in which said testing equipment
is positioned adjacent said second conveyor and is relatively
moveable along the path thereof, the positioning of said testing
equipment being predetermined and based upon the number of reaction
tubes in said plurality of reaction tubes for each specific
sample.
25. For use in an automatic chemical analysis apparatus, a pipette
apparatus which comprises a pair of electrically conductive
members, one of said pair being a tube through which sample can be
drawn from containers, said members being electrically insulated
from each other and mechanically linked to one another so as to be
moved as a unit relative to the level of the sample within a sample
container and be placed in physical and electrical contact with the
sample, said tube member having a lower end which extends a
determinable distance beyond that of said other member into the
sample, and an electrical conductor connected to each said member;
whereby, when said pipette is immersed into the sample said
determinable distance, a responsive electric signal can be derived
from said conductors.
26. Apparatus according to claim 25 in which said conductive
members are adjustably linked to one another for varying said
determinable distance.
27. Apparatus according to claim 26 in which said other member also
is a tube and surrounds said sample drawing tube for most of its
length, except for said determinable distance.
Description
The invention relates to apparatus which automatically makes a
plurality of chemical tests on a series of individual samples which
are fed to the apparatus.
Apparatuses of this type are known particularly in the medical
field. For the purposes of lucidity and ease of understanding, the
invention will be described in detail as used in the medical field,
but it should be understood that the invention is not so
limited.
In the medical field, for diagnostic and routine informational
purposes, and often for research, certain chemical tests are
performed on samples of whole blood or blood serum. Often physical
tests are additionally performed on the samples. Classically all
such tests were performed manually by trained technicians in
laboratories. In a typical chemical test, the patient's blood would
be drawn, spun in a centrifuge to separate the serum from the
cells, the serum decanted and placed in a container suitably
identified with the patient's identification data. The technician
would then measure out a small quantity of serum into a reaction
tube, mix the serum with a precise proportion of some chemical
reagent, mix this thoroughly, place the reaction tube in a water
bath maintained at some precise temperature and time its presence,
i.e. incubation, in the bath in accordance with the type of test
being conducted. This incubation period is sufficient to achieve a
certain chemical reaction which will change the color of the
diluted specimen. Then the technician would remove the reaction
tube from the water bath, pour a quantity into a cuvette, direct a
beam of light at some predetermined wave length through the cuvette
and measure the absorbance of the light in the solution in the
cuvette. This latter operation could be performed in a
spectrophotometer or other colorimeter.
Over a period of years, these chemical tests have developed to a
relatively high degree of acceptance to ascertain such information
as the total protein of the blood; the presence of certain
chemicals such as phosphorous, potassium, sodium, and calcium; the
amount of creatinine in the blood; the amounts of different
enzymes, albumin, etc. Laboratories may perform as little as one or
two tests on the available specimen or as many as twenty. The
reagent composition, the proportions, the incubation time, the
temperature of incubation time and the wave length of the incident
light passed through the end solution vary from test to test.
Certain problems are inherent in the manual execution of these
tests by technicians and the obviation of these problems is the end
sought by most automated or semi-automated automatic chemistry
apparatus.
Among the problems associated with manual performance of these
tests are the likelihood of human errors promoted by the
measurements which must be made manually, the need for entering
information and data relating to the sample and keeping its
identification straight, tediousness and fatigue of the technician,
errors in choosing the proper chemicals and the failure to keep the
equipment clean of contamination. Other disadvantages in the
classical methods are loss of time, expense, waste, etc.
The known automatic chemical analysis apparatuses solve the above
problems in varying degree, although not all apparatuses solve all
problems. These apparatuses take different forms. Some apparatuses
include turntables that rotate samples to a sample withdrawing
position. At the sample withdrawing position, the samples are
diluted and passed to the processing portion of the apparatus. In
one form of apparatus, the diluted samples are passed through
conduits one after the other, separated by quantities of diluent
and bubbles. In other systems, the diluted samples are carried in
reaction tubes on continuous drums or conveyors. In one apparatus a
plurality of tubes are mounted on racks, are incubated in a bath
and are moved into and out of the bath by chains engaging the
racks.
Known automatic chemistry analysis apparatuses have problems, the
solutions of which have made such devices complex, expensive,
overly large in size and in some instances likely to produce
erroneous results. Of importance in the problems are patient
indentification and contamination. Some of these apparatuses are
continuous and require that all tests be performed on all samples.
The apparatus to be described hereinafter provides for selective
performance of tests and hence is economical. It also maintains
patient identification with relation to tests and test results and
provides for efficient cycling of reaction tubes through the
apparatus.
Accordingly, the invention provides an apparatus for automatic
chemical analysis comprising a first sequentially advanceable
conveyor for carrying containers holding samples to be tested, a
second sequentially advanceable conveyor carrying reaction tubes in
which chemical reactions can be caused to occur, first and second
stations fixedly positioned along the path of said first and second
conveyors, respectively, transfer structure positioned adjacent
said first and second stations for sequentially transferring
portions from each container when it is at said first station to a
predetermined plurality of the reaction tubes as they are moved
past said second station, apparatus capable of adding different
reagents to each of said plurality of reaction tubes, a programmed
drive arrangement for advancing said first conveyor to present a
next sample container to said first station in conjunction with
advancing said second conveyor to present a next plurality of
reaction tubes sequentially to said second station for sample
transferring, and testing equipment for testing the reaction
products of each of said plurality of reaction tubes.
Features and advantages of the invention will become apparent from
a study of the following description of an embodiment thereof when
taken in conjunction with the accompanying drawings in which:
FIG. 1 is a perspective view of an apparatus for automatic chemical
analysis;
FIGS. 2a and 2b show a top view of the apparatus shown in FIG.
1;
FIG. 3 shows a piercing device for said apparatus;
FIG. 4a is a section of the sample container used in the
apparatus;
FIG. 4b is a perspective view of the said sample container;
FIG. 4c shows the label for said sample container;
FIG. 5 shows the upper portion of a transfer pipette used in the
apparatus;
FIG. 5a shows a section along the line X--X of FIG. 5;
FIG. 6 shows the lower portion of a transfer pipette used in the
apparatus;
FIG. 6a shows a section along the line X--X in FIG. 6;
FIG. 6b shows a section along the line Y--Y in FIG. 6;
FIG. 7 shows the pipette used in the apparatus;
FIG. 8 shows a valve mechanism and pump;
FIG. 9 shows the operating mechanism for said pump;
FIG. 10 shows the colourimeter head assembly;
FIG. 11 shows another view of the colourimeter head assembly;
FIG. 12 shows the cuvette for use with said colourimeter head
assembly;
FIGS. 13a, b, c and d are block diagrams of the electrical system
of the apparatus;
FIG. 14 shows waveforms of signals appearing at various points in
the system of FIG. 13;
FIG. 15 shows diagrams explanatory of the operation of the sample
transfer and wash means;
FIG. 16 is a diagram showing the liquid flow in the apparatus;
FIG. 17 shows the identification device;
FIGS. 18a and b are block diagrams of the electrical system of the
colourimeter;
FIG. 19 shows waveforms of signals appearing at various points in
the system of FIG. 18;
FIG. 20 is a circuit diagram showing the main timer;
FIG. 21 is a circuit diagram showing the colourimeter timing
control;
FIGS. 22a, b and c are circuits explanatory of the operation of the
measurement system of the colourimeter; and
FIG. 23 is a graph showing the operation of the system of FIG.
22.
In broad terms, the apparatus to be described hereinafter transfers
a portion of the test liquid contained in a sample container to a
reaction tube, preferably together with a suitable diluent, adds a
reactant appropriate for the constituent of the sample which it is
intended to detect, transfers a portion of the resulting liquid to
a test cuvette and subjects it to colourimetric analysis. The
result of this analysis provides a quantitative determination of
the amount of substance, sensitive to the particular reactant,
which was present in the sample. The apparatus is suitable, for
example, for measurement of various constituents in whole blood,
plasma or serum (such as glucose, urea, albumen or total protein
content), milk, beer, or sewage. Whilst in the apparatus described
herein colourimetric analysis is utilised, it will be evident that
the solution after treatment with the reactant may alternatively
where appropriate be examined by other means, such as particle
analysis, fluorescence analysis, or ion measurement thereby to
provide a quantitative determination of the constituents.
The apparatus to be described is capable of carrying out six tests
on each of 40 specimens per hour. Alternatively, it may be
programmed to carry out five, four, three or two tests on each of
the specimens; this will lead to correspondingly higher specimen
throughputs. The portion of liquid transferred to the reaction tube
is from 25 to 50 microlitres and the amount of diluent is 250
microlitres. The amount of reagent used is 2.5 millilitres. After
incubation with the reagent the developed colours are measured
using a separate colourimeter for each test, and the results are
printed out in concentration terms together with a six digit
specimen identification number. For each test, a reagent is chosen
which will produce a reaction product which absorbs light.
Referring to FIG. 1, there is shown a perspective view of a
complete apparatus in accordance with an embodiment of the
invention. It is housed in a cabinet 1 occupying a floor space of
approximately 90 cm .times. 70 cm. The samples to be analysed, in
containers 21, are carried on a belt 2 which is stretched around
motors and idler wheels 12 arranged in a rectangular pattern. The
belt 2 is advanced in steps so that each sample container 21 in
turn stops at a datum point where a sample of the liquid in it is
transferred by a transfer means 33 to a test tube carried by a
reaction loop belt 5. At the same time a diluent, for example
water, is also added to the test tube. Samples from one tube 21 are
added to two, three, four, five or six of the test tubes carried by
the belt 5, the number being selected by pressing the appropriate
button on the control panel 13. At a selected station, as the
reaction loop steps round the closed path, suitable reagents are
added to the test tubes and the resultant mixture examined by the
colourimetric analyser 41. At a later stage in the path round the
loop the tubes are washed by a cleansing apparatus 15 and then
returned to the initial point where they can take part in further
reactions. The pumps for pumping the reagents, or reactants, into
the reaction tubes are contained within the cabinet as shown at 7.
The containers for the supplies of reagents are shown at 9, and the
containers for the washing water and the waste extracted after
washing the tubes are shown at 8. The result of the colourimetric
analysis is printed out on to a roll of paper as may be seen at 10.
The results from the tests on the two, three, four, five or six
specimens from each sample, and relating to different constituents,
are printed sequentially and the device 4 contains means for
setting identifying letters so that, for example, the measurement
of glucose in blood can be prefixed in the print-out by the letters
"GLU". The printing mechanism for indentification is set by the
operator in accordance with the tests which the machine has been
set to perform. Additionally, the result of the analysis together
with the identifying letters are available at a terminal for
connection to a central processing means.
The horizontal upper surface of the apparatus 1 is shown in greater
detail in FIG. 2 in which 20 indicates the upper surface of the
cabinet. A plastics belt 2 is carried in a substantially
rectangular path around pulleys 12 which are driven by electric
motors or idlers. The outside of said belt 2 carries mounts similar
to those in a test tube rack whereby sample containers, which will
be described in more detail hereafter, can be placed, as for
example as shown at 21. When the motor is operated the sample
containers advance, carried by the belt 2 in an anticlockwise
direction, until a container at a station 32 is opposite the
microswitch 22 which operates mechanism to stop the belt. In
subsequent operations, after the belt has been re-started, it
advances until the container adjacent the container in the belt
which was at station 32 occupies station 32, and again the
microswitch 22 operates to stop the motors. In this way the belt
advances by an amount equal to the distance between sample
containers at each step in the operation. It will be appreciated,
therefore, that in the operation of the machine the first step is
to load the carriers on belt 2 with containers containing the
samples to be tested. In the machine described herein there is
space for 100 sample containers.
The reaction loop 5 is similar to that associated with belt 2 but
is fitted with tubes such as 23 in which reactions can take place.
Otherwise it is provided with motors and idlers 24 corresponding to
elements 12 and a microswitch 25 corresponding to element 22.
The apparatus is also provided with an inner reaction loop, not
visible in FIG. 1, similar to the reaction loop 5 but located still
further to the centre of the upper deck. This comprises a belt 26
carrying test tubes such as 27 round two pulley wheels 28. It is
surrounded by a wall 29 and is provided with a heater element 30.
The purpose of the inner reaction loop is to provide an environment
in which reactions which may be required to take place at a
different temperature from those in the outer reaction loop 5 may
be effected.
Now, considering the operation of the machine, after the outer loop
2 has been loaded with sample containers containing the samples to
be tested, a device 31 is provided which as each container comes to
rest at its station penetrates the cap of the sample container to
cut an X-shaped incision. This is effected so that subsequent
operations in the transfer of liquids from the container may be
accomplished more readily.
The device 31 is shown in greater detail in FIG. 3. The device
comprises a cover 60 mounted on a substantially L-shaped support
frame 61. A solenoid 62 is slidably mounted on said frame 61 by
means of a screw device 63. This enables adjustment of the height
of the solenoid to be effected. The cutting head 64, having an
X-shaped cutting means is mounted in said solenoid so that
energisation of the solenoid causes the cutting head to be driven
downwards. The device 31 is mounted in such a way that the belt 2
carrying the sample containers such as 21 passes through device 31
with the containers passing immediately below the cutting head 64.
With a container 21 accurately located under the cutting head 64,
the solenoid can be energized so as to drive the cutting head 64 to
penetrate the cap of the sample container, cutting an X-shaped
incision therein. Alternatively, instead of utilising a solenoid to
drive the cutting head 64, it can be driven by an electric motor
through a rack and pinion gear.
After the containers have progressed a further two steps around the
loop 2, a container with a cap having an X-cut appears at the
station 32. Whilst the sample container is stopped at this station
a device 33, to be described in more detail hereafter, which
comprises a pipette carried on a horizontally swinging arm is
positioned over the sample container, lowered into the sample
container, extracts 25 to 50 microlitres therefrom, is raised,
swung over to the inner reaction track until it is above the
reaction tube shown at 34, and transfers the portion of the sample
thereto, referred to as an aliquot, adding also a predetermined
quantity of diluent such as water. With the outer belt stationary
the inner reaction belt 5 moves one step along until another tube
occupies the position 34 and the process is repeated so that
another portion of the substance in the same sample container is
transferred to another reaction tube. According to the setting on
the control panel 13 this is repeated until there are two, three,
four, five or six tubes on the reaction loop all containing
aliquots of the material from the sample container at the station
32. When this has been accomplished the belt 2 moves one step along
to present another sample at the station 32 and the process is
repeated. If the inner reaction loop is also to be used a similar
transfer is made by the device 35, similar to the device 33, which
transfers material from a sample container at the station 36
transferring it to a reaction tube on the inner belt 26 at the
station 37.
As the tubes on the reaction loop 5 move around the loop one step
at a time, they reach a position under a head 38 comprising six
discharge nozzles for reactants, and at this point whilst they are
stationary the appropriate respective reactants are added to the
two, three, four, five or six reaction tubes. These, or additional
discharge nozzles, may alternatively be placed at other points in
the loop. Subsequently after several further steps the tubes reach
a position under a colourimetric head 39 wherein the colourimetric
analysis of the reaction products in the respective tubes occurs.
As already indicated the result of this measurement is printed out
on to the roll of paper at 10 (FIG. 1). At a later stage in the
progress round the loop 5 the tubes reach a position under a
washing head 40 where the liquid in the reaction tubes is
extracted, rinsing water added, the tube emptied, a second rinse
added and the tube then emptied. The tubes then as they progress
around the loop 5 repeat the cycle with samples extracted from
other sample containers in the loop 2.
A similar operation occurs in the inner reaction loop wherein the
reaction tube 27 passes under a head 41 where a reactant solution
is added. A colourimetric analysis is performed corresponding to
that accomplished in connection with the device 38 by means of a
colourimetric head 43.
The liquid flow involved in these operations, excluding the
colourimetric testing, is shown symbolically in FIG. 16. The sample
containers are shown at 900, and a pipette 901 of the device 33
(FIG. 2) extracts a test portion from the sample container by the
operation of the syringe 902. This is transferred to one of the
reaction tubes at 905 after the pipette 901 has been swung into
position thereabove. Diluent contained in the container 903 is also
transferred through pipette 901 to said reaction tube, by means of
the pump 904, to be described in detail hereinafter. This is
repeated as many times as required. The test reagents are contained
in the containers 906a, 906b, 906c, only three such systems being
shown in the Figure for the sake of clarity. The reagents are
transferred through the valves 907a, 907b, 907c by the operation of
the pumps 908a, 908b and 908c through valves 909a, 909b, 909c and
the discharge nozzles 910a, 910b, 910c into the reaction tubes.
After colourimetric analysis the contents of the test tube in the
line 905 are removed through a tube 911, a sediment trap 912 and a
valve 913 by the operation of pump 914 through valve 915 and an
anti-siphon trap 916 to a container 917 for waste. Sediment from
the sediment trap 912 falls through a tap 912a into a waste
container 917a. A rinsing liquid from a container 918 is then
pumped through valve 919 by means of pump 920 through valve 921 and
by means of T-junction 922 along tube 923 into the reaction tube.
This rinsing liquid is then removed along tube 924 through valve
925 by means of pump 926 through valve 927 to the siphon trap 916
and waste container 917. The rinsing process is then repeated,
utilizing again liquid from container 918 which is applied by means
of pump 920 along tube 928 into the reaction tube. Finally, the
rinsing liquid is removed along pipe 929 through valve 930 by means
of pump 931 through valve 932 into the anti-siphon trap 916 and
waste container 917.
The sample container for use with the apparatus described above is
shown in FIGS. 4a and 4b which respectively show a section a
perspective view thereof. The container comprises a portion 101, in
the shape of a test tube made of a transparent or translucent
material. It is provided with a thickened base portion 103, the
outer edge 104 of which is cogged. There is a circular indentation
in the bottom 105 of said base 103. An identification label 106 to
be described in more detail hereafter is adhered to the outside of
the tube. It is preferred that the label does not completely
encompass the tube in order that the contents may be visible. A cap
102 of suitable elastomeric plastics material is provided. The belt
2 is provided with rack means 220, 221 (FIG. 5) for supporting the
sample container and the depression 105 is adapted to engage with a
pin member 222 (FIG. 5) on the rack so that the tube may be rotated
by means of a toothed wheel 108 (FIG. 17) which engages with the
cogged edge 104. The purpose of this will appear subsequently. It
will be obvious to those skilled in the art that other means may be
utilized for rotating the tube. The label is shown in FIG. 4c and
comprises a matrix of six columns each containing the numbers zero
to nine printed on a highly reflective sheet. Along the left-hand
edge is a column in which portions corresponding to the lines 0, 2,
4, 6 and 8 are blackened. Along the top there are blackened
portions corresponding to each column. When a sample has been put
into the container it is identified by a six-figure number and this
is indicated by blackening appropriate portions in each column
using a suitable dark ink. The squares containing the numbers are
separated by portions which tend to inhibit the ink from spreading
into an adjacent square. The label shown in FIG. 4c is intended to
indicate the identification number 356635.
The mechanism for operating the transfer pipette 901 in FIG. 16
(the device 33 of FIG. 2) is illustrated in FIGS. 5 and 5a.
Referring to FIG. 5 which illustrates the portion of the mechanism
appearing above the deck 20, the outer band 2 is shown carrying a
sample container 200 and the band 5 carrying a reaction tube 201 is
shown. The pipette tube 202, which will be decribed in greater
detail subsequently, is mounted on an arm 203 carried on a rod
member 204 which is capable both of rotary movement and
longitudinal up and down movement. Thus it is possible for the
member 204 to lower the pipette 202 into the sample container 200,
raise and then rotate the pipette into a discharge position over
the reaction tube 201. The arm 203 is shown in more detail in the
plan view of FIG. 5a from which it will be seen that the arm is
capable of adjustment by means of a slot 230 in the end of said arm
203 which is clamped by a bolt 231 to allow the position of the
pipette to be adjusted.
Referring now to FIGS. 6, 6a and 6b, which show the side view and
sections along lines X-X and Y-Y of FIG. 6 of the part of the
mechanism below the deck 20, it will be seen that the member 204 is
continued below the deck 20 and is attached by thrust collars 205
to a parallel member 206 provided with a rack engaging with a
pinion 207 geared to an electric motor 210. Operation of the motor
210 causes the member 203 to be raised or lowered. Limit switches
208 and 209 are provided in order to allow the extent of the
raising to be controlled and to prevent the mechanism lowering the
pipette too far in the absence of a sample container 200. Rotation
of the member 204 is accomplished by means of the motor 210 which
is geared to the member 204. As in the case of the raising and
lowering, limit switches 211 and 212 are provided which are
adjustable to control the movement of member 204 so that the
pipette can be lowered accurately both into the sample container
200 and the test tube 201. The member 204 is provided with a groove
213 which engages with a pin 214 in a tubular member 215 which is
coupled to the rotation motor 210. This enables the rotation
movement to be transmitted from the drive 210 to the member 204
irrespective of the vertical position thereof.
The pipette is shown in greater detail in FIG. 7 and comprises a
gold-plated stainless steel tube 300 of 2 mm outside diameter
provided with a bore. The outer diameter tapers to 1 mm within a
brass cylindrical member 301 of 5 mm diameter and 5.5 mm length
which encompasses said tube 300. Immediately below said member 301
is a black nylon washer 302 of 10 mm diameter and 1 mm thickness in
contact with said member 301 and surrounding the tube 300. Below
the washer 302 a stainless steel tube 303 of 2.4 mm outside
diameter is slipped over tube 300 but is electrically insulated
from said tube 300. 5 mm below the washer 302 is a 10 mm diameter
brass washer 304 1 mm thick which makes electrical contact with
tube 303. The portion of the tube 303 which extends below washer
304 is 66 mm in length and tube 300 projects 2 mm beyond the end of
tube 303. Electrical connections 305 and 306 are made to the
cylindrical member 301 and the washer 304 respectively. A flexible
plastics tube 307 is attached to the top of the pipette whereby
vacuum can be applied to the pipette to suck liquids up into it and
pressure can be applied to blow them out again. The purpose of the
electrical connections 305 and 306 is to provide an indication when
the pipette has entererd 2 mm below the surface of the liquid in
the sample tube 200 (FIG. 5). The liquid forms an electrical
connection between the conductors 305 and 306 and this can be used
to operate a relay which prevents further descent of the pipette
into the liquid. This is of particular advantage when the sample in
the container is a blood sample which has been centrifuged to leave
the plasma in the upper portion of the container. By this method
samples of the plasma only are extracted for analysis.
It will be appreciated that both the device 33 (FIG. 2) and the
device 35 (FIG. 2) utilise the construction illustrated in FIGS. 5,
6 and 7.
The pump for transferring liquids from one container to another is
illustrated in FIG. 8. It is constructed principally of glass
tubing and referring to FIG. 8 the portion 400 is the barrel of a
hypodermic syringe but the piston of said syringe 401 is formed of
a Teflon (Registered Trade Mark) member having a shape such as
shown in the Figure. The advantage of this shape is that the fit of
the piston is less affected by temperature than would otherwise be
the case. The drive to the piston is a rod 402 the operating
mechanism of which will be described below. A T-junction of glass
is sealed to the end of the barrel 400 and to that is sealed a tube
412 which has a narrow bore at each end and opens into a wider
portion at the centre. A plug 405 having a conical end as may be
seen in the Figure is provided within said tube 412 A constriction
406 is provided in tube 412 to limit the movement of the plug 405.
A tube similar to 412 is attached to the remaining outlet of the
T-junction 403 and contains a plug 409. A constriction 410 is
provided to limit the motion of the plug 409. The end of the
last-mentioned tube containing the plug 409, identified as 411 in
the Figure, is connected to the source of liquid and the end of
tube 412 shown as 407 in the Figure is connected to a pipette. In
operation, and starting with the piston 401 at the upper part of
its travel, as it is drawn down by motion of the member 402 the
plug 405 is forced against the edge 404 sealing the tube 407 and
the plug 409 is raised upwards allowing liquid from a first
container to be drawn through 411 into the barrel of the syringe.
On reversal of the movement of the piston the plug 409 is forced
against the edge 408 closing off the path to said source and the
plug 405 is raised allowing the liquid to be forced out through the
tube 412 to the exit 407 connected to a pipette or discharge
nozzle.
The operating mechanism for the piston 401 in FIG. 8 is shown in
FIG. 9. It comprises a drive pinion 500 coupled to a rack 503 on
the member 402 which connects with the piston 401. The drive pinion
500 is coupled to an electic motor through a friction clutch drive.
A staircase shaped member 501 is located in such a position that
the end of rod 402 will engage with one of the steps of said
staircase when the piston is at its intended lower limit of travel.
Movement of the staircase sideways in the Figure is used to control
the extent of the descent of the piston 401 to control the quantity
of liquid which is drawn into the syringe. A member 502 is attached
to rod 402 in such a position that at the intended limit of upward
travel of the piston it engages with a stop 504. It has been found
that the sudden stopping of the piston produced by the member 502
striking member 504 is effective to prevent drops forming on the
end of the pipette.
The colourimeter head assembly is illustrated in FIG. 10.
Essentially it is an arrangement whereby light can be directed
through the samples of liquid after an appropriate reagent has been
added thereto, through an optical filter, to a photocell. The
output of the photocell provides a quantitative indication of the
amount of a particular constituent in the solution. The assembly
shown in FIG. 10 provides means for testing six samples
simultaneously which have been subjected to differnt reagents so
that each gives an indication of a different constiuent. Light from
a light source 602 is directed into six fibre optics paths such as
601 which carry the light to six test points. Samples of the liquid
are contained in a cuvette into which the liquid is drawn. One of
the six optical filters is shown at 603 and a respective photocell
at 604. Thus light passes from the end of the fibre optics tube 601
through the cuvette at 600, through the optical filter 603 to the
photocell 604. It will be seen that the six photocells are arranged
alternately on each side of the path along which the reaction tubes
are travelling. The reason for this is that the dimensions of a
photocell are larger than the separation between successive
reaction tubes. By arranging them in the staggered manner as shown
it is possible to accommodate them in the space available. A
similar arrangement but comprising only one test path is provided
for the inside reaction loop at 43 (FIG. 2).
Another view of the optical arrangements associated with the
colourimetric test portion of the apparatus is shown in FIG. 11.
The light source 602 comprises a 6-volt, 10-watt tungsten halogen
projector lamp 610, which is supplied from an accurately stabilised
regulated power supply 611. The lamp is provided with a surface
silvered dichroic semi-ellipsodial reflector 612 constructed to
transmit heat energy above 1,000 nm, and to reflect light energy
below 1,000 nm. This minimizes heat transfer from the lamp 610 to
the colourimetric block 614, even at quite high levels of
illumination. The lamp and reflector may be adjusted in relation to
each other and the lamp is positioned so that the filament is at
one focus of the reflector ellipsoid. An approximately equal amount
of light from the lamp is transmitted to each of the six
colourimeters along the fibre optic paths 601, one of which is
shown in FIG. 11. A black nylon rod 613 is threaded at 615 into the
block 614 so that it protrudes into its respective light path
between the fibre optics path 601 and the cuvette 600. It is used
as a coarse adjustment of the output of the photo cell 604, so as
to bring this within the range of the electronic circuitry. The
cuvette will be described in more detail below in connection with
FIG. 12. After passing through the cuvette 600, the light passes
through a filter 603 carried by a filter holder 605. The filter is
an interference filter, having a half band width of approximatley
10 nm. It is desirable that for each test a filter is selected such
that its pass band coincides with the maximum absorption due to the
reaction product.
It will be observed that the colourimetric testing is performed in
cuvettes separate from the reaction tubes rather than utilizing the
reaction tubes themselves for this purpose. The reason for this is
that the reaction vessels are optically inadequate for precise
colourimetric analysis. It is economically preferable to provide a
small number of optically adequate cuvettes than a much larger
number of optically adequate reaction tubes. Furthermore, by
utilizing a plurality of cuvettes, each one can be employed
exclusively for its own chemical analysis and therefore be adapted
to and connected to its own sampling probe.
The cuvette for containing a sample to be tested in the
colourimeter is shown in FIG. 12. It comprises a tube 700 of Pyrex
(Registered Trade Mark) glass, opaque to light of wavelength
shorter than approximately 380 nm, narrowed at one end and sealed
to a bored metal tube 701. The other end is also narrowed at 702. A
plastics bored plug 704 is forced into the end 703. The tube
contains a plug 705 which is provided with a conical portion 706
which engages with a conical portion 707 of the tube. The portions
706 and 707 are ground together during construction.
One end of a length of flexible tube 708 is connected to said tube
701 and a length of stainless steel tube 709 is connected to the
other end of said flexible tube 708. In an alternative arrangement
the flexible tube 708 is connected directly to the tube 700, the
metal tube 701 being omitted. In use the end of tube 709 is lowered
into the reaction tube containing the solution to be examined until
the end of the tube 709 is below the surface of the liquid in said
reaction tube. Vacuum is applied through a pipe to the member 705
and this causes the plug 705 which has been at the bottom of the
tube under the influence of gravity to be drawn upwards drawing
liquid into the tube. When the plug reaches the top of the tube it
closes the vacuum line so as to prevent further liquid being drawn
into the apparatus. It remains in this position whilst the tests
are being made. After the tests have been made pressure is applied
to the member 704 causing the plug 705 to drop forcing liquid out
of the tube 709 back into the test tube. When the plug reaches the
bottom of the cuvette there is sufficient leakage of air past the
sides of the plug 705 to force any remaining liquid out of the tube
709. To ensure said leakage of air past the base of said plug 705,
two pips 710 are provided in the base of said tube 700. With the
cuvette empty the float 705 rests in the light path reducing the
intensity of light reaching the photocell.
At the same time as a test is being made on two, three, four, five
or six of the test tubes on the reaction loop 5 and possibly also
on the inner reaction loop 26 it is necessary to identify the
sample container from which the sample was taken.
To minimize the need for equipment to read, store, transfer,
compare, etc. each sample container identification with the
identification of the several reaction tubes for each sample
container and the associatd colourimetric test results for each
respective aliquot, the relative physical positions along the belts
2 and 5 of the sample containers, reaction tubes, and the
colourimeter head 39 are flexibly predetermined with respect to the
position of a relatively movable sample identification station 42,
shown in FIG. 2a adjacent the sample container belt 2. Quite
simply, for positive and direct identification of a sample and its
aliquot test results, a sample container 21 is to be positioned at
the identification station 42 when all of the aliquots from that
sample are in the colourimeter station 39. Normally, the
colourimeter station 39 will encompass the 43rd to 48th step
positions of the reaction tubes on the belt 5 from the transfer
point 34 (as shown in FIG. 2b). Since 48 divides evenly into 2, 3,
4 and 6, the first aliquot of a sample will have arrived into the
48th step position in the belt 5 with the arrival of its sample
container at the 24th, 16th, 12th or 8th step position along the
belt 2 from the transfer point 32, depending upon the number of
aliquots per sample, i.e. two, three, four or six, respectively. If
there are to be five aliquots per sample, the colourimeter station
39 is moved two steps further, such that its end at the 50th step,
and the sample identification station 42 is positioned at the 10th
step.
For example, if each of a series of samples are to undergo the same
four tests, such tests will be programmed by way of the control
panel 13 and the printer control 4. The identification station 42
will be positioned adjacent the 12th step (48 divided by 4) from
the transfer point 32 and the colourimeter 39 will encompass
positions 43 to 48. When any specific sample container reaches the
identification station 42, its four aliquot tubes will be in step
positions 49 to 45, such that the corresponding four cuvettes 600
will receive and provide the colourimetric test reactants for data
recording. Such data recording will receive the sample container
number identification of the sample container then in the
indentification station 42.
In FIG. 17 the identification device 42 is shown with a sample
container 101. When the sample to be identified reaches the
identification station it engages with a pinion 108 which is set in
motion to cause the sample container to rotate about its
longitudinal axis by engagement with the cogging 104. The
depression in the base 105 (FIG. 4a) serves as an axis of rotation.
A vertical column of eleven fibre optics bundles is arranged so as
to line up accurately with the columns of identification on the
label 106 (see also FIG. 4c). A portion of each of the bundles goes
to a light source and the remaining portion of each of the bundles
goes to separate photosensitive devices so that indications can be
provided as to whether the device is "seeing" a blackened portion
of the label or a reflective portion of the label. On the rotation
of the container the print-out mechanism for printing out the
identification ignores all indications until a unique code
combination on the photosensitive devices corresponding to the left
column of the label is received. This provides the information that
the rotation of the container has brought the left-hand side of the
label opposite the detection device. Subsequent indications are
registered, being gated by pulses obtained from the unnumbered top
line of blackening so that the columns are read in succession.
These indications are fed to a printer which prints out the number
which has been read on the printing mechanism 10 (FIG. 1) followed
by the indications from the indicators 4 and the respective outputs
of the photocells 604 (FIG. 10).
The electronic and electrical system which controls the operation
of the aapparatus is shown in block form in FIG. 13, the waveforms
appearing at various points in the system being shown in FIG. 14.
Portions FIG. 13a of the diagram shows the circuit which controls
the main timer. The reference numerals in FIG. 13 are the same as
used in FIG. 20 which shows various parts of the electrical system
in greater detail. At rest, before the apparatus is switched on, a
line identified as carrying the waveform d (see FIG. 14) applies a
potential of 5 volts, the output of a bistable trigger 803, 803a,
to a relay 711. The potential is also applied to an oscillator 800
in such a way as to prevent oscillations being generated and to a
counter 801 to reset said counter. Oscillator 800 when oscillating,
generates oscillations as shown in waveform 14b having a period of
1.5 seconds. The potential applied to relay 711 energises said
relay and allows a potential of 24 volts to be applied through a
switch 711', which is closed as will appear subsequently when a
transfer has been completed from the diluent pump, and a start
switch 712 on the front panel of the apparatus to a relay 713.
Energisation of relay 713 allows power to be supplied to the motor
24 wich drives the belt 5 (FIG. 2) which carries the reaction
tubes. It will be appreciated that the belt 5 starts to move when
the start switch 712 has been closed. The motor 24 carries a cam
714 adapted to operate two microswitches 741', and as soon as the
motor begins to turn one of said microswitches applies a potential
of 24 volts to said relay 713 so as to keep said motor 24
revolving, and thee other microswitch changes the voltage on a line
identified as a (waveform 14a) from 5 volts to zero volts. Said a
line is connected through an inverter 715 to said bistable trigger
803, 803a and to a bistable trigger 810, 808, to change both their
states. Said bistable trigger 810, 808 is utilized to clock a
counter included in the test counting system and provides a half
cycle command output. The bistable trigger 803, 803a allows the
oscillator 800 to commence oscillating and removes the reset from
counter 801. When said counter 801 reaches a count of four, the
bistable trigger 810, 808 is reset and this removes the half-cycle
command output. When said counter 801 arrives at a count of eight,
the bistable trigger 803, 803a is reset and this replaces the clamp
on oscillator 800 to prevent it oscillating, resets said counter
801, and energizes relay 711. This completes a cycle for the belt 5
of which the duration is approximately 15 seconds. An output from
bistable trigger 810, 808 is applied along the line c (waveform
14c) as one input to an AND-gate 808' of which the other input is
the waveform a from one of the microswitches 714'. The output of
said AND-gate 808' appears at a terminal 809 and is applied to a
relay 716 which controls sample transfer and washing, as will be
described subsequently.
The test counting system is shown in FIG. 13b. A counter 811 is
connected to an output of bistable trigger 810, 808 (FIG. 13a).
Said counter 811 has five output terminals and a signal such as f
(waveform 14f) appears successively on each of these when 2, 3, 4,
5 and 6 tests have been made on a sample. The respective outputs of
counter 811 are applied to the contacts of a switch 812a in the
panel 13 of FIG. 1. According to the position in which said switch
is set, a signal will appear on the output of the switch when a
predetermined number of tests has been accomplished. The output
from counter 801 (FIG. 13a) which triggers bistable trigger 810,
808 is also applied to a bistable trigger 815, 816 as a reset.
Said counter 811 also obtains a reset signal through terminal 813
which is the output of an OR-gate 720 which has one input derived
from a transport microswitch 721' and the other input derived along
a line g (waveform 14g) from a microswitch 722 operated by a cam
722' connected to the drive motor 12 for the sample container belt
2 (FIG. 2). The output of bistable trigger 815, 816 is supplied as
one input of an AND-gtae 723 of which the other input is a signal
obtained from the microswitch 714' (FIG. 13a) on line a (waveform
14a), through an inverter 724. The output of gate 723, waveform 14h
is applied to the colourimetric timing system to start said system
as will appear subsequently. The output from switch 812a is applied
as one input to an OR-gate 725 of which the other input is a signal
derived from microswitch 721' and also along line g from
microswitch 722 through an inverter 726. The output of said gate
725 is applied as one input of an AND-gate 727 of which the other
input is the output of an OR-gate 728 which has at its inputs a 24
volt signal from switch 721' and a 24 volt signal from a start
switch 729. The output of AND-gate 727 is applied to a relay 730
which controls the power to energize the belt drive motor 12 for
the sample container belt 2. Another output of the bistable trigger
815, 816 is applied to line e (waveform 14e) as a timing command
signal to the reagent sub-system which will be described
subsequently. In operation, supposing a "four-test" is selected on
switch 812a, at the end of four cycles of the belt 5, relay 730 is
energized thus driving the belt 2. As the sample belt moves, the
microswitch 722 is released and reactuated. This will stop the main
sample drive motor 12, reset counter 811 and set bistable trigger
815, 816. This issues a start command to the colourimetric
mechanism timing system. A start command is also taken from the
wiper of switch 812a along line 731 to initiate operation of the
identification system of FIG. 17.
The sample transfer system is illustrated in FIG. 13c. To the right
of the Figure is shown the arm 203 carrying the pipette 202 (see
FIG. 5) which transfers portions from the sample container to the
reaction tubes 905 (see FIG. 16). The syringes 902 for the aliquot
and the diluent pump 904 are also shown. The transfer system is
operated in response to signals from relay 716, also shown in FIG.
13a, which is energized by a half cycle command signal as was
described in connection with FIG. 13a. During the first half-cycle
said relay 716 is energized and passes a 24 volt signal to a relay
740. This relay initiates two functions: first the diluent pump is
charged with diluent by operation of a means 741, and second, the
probe 202 is rotated by a means 742 until microswitch 212 is
released. This energizes a relay 743 which causes the probe to be
lowered by a means 744. The lowering continues until either, if the
sample tube is empty the probe travels down until microswtich 209
on the member 204 is actuated, stopping the action of the
probe-down means 744 or until a liquid surface is sensed which by
means of the probe contacts via means for adjusting the sensitivity
745 operates said relay 743 again stopping the downward travel of
the probe. Operation of said relay 743 energizes a means 746 causes
charging of the aliquot syringe 902 so that the probe picks up a
portion of the sample. The system now waits for the half cycle
command from the circuit of FIG. 13a to de-energize relay 716. When
this happens, a relay 747 is energized, causing operation of a
means 748 for raising the probe. The upward motion continues until
microswitch 208 on member 204 is operated to release relay 747 and
energize a relay 749. Said relay 749 causes operation of a means
750 which rotates the probe back towards the central loop until
microswitch 211 is released. This allows energization of a relay
751 which operates a means 752 which causes the aliquot to be
discharged until microswtich 755 on said aliquot syringe 902 is
actuated. This energizes a relay 753 which operates a means 754 for
causing the diluent pump 904 to be discharged. When the diluent is
fully discharged microswitch 711' is actuated. Said microswitch is
the switch 711' in the circuit of FIG. 13a, and its operation
enables the reaction tube belt 5 to be driven on when the main
timer circuit is ready.
The successive steps in this operation are illustrated in the
diagram of FIG. 15, where (a) shows the half-cycle command signal
to the relay 716, (b) shows the relative up and down position of
the diluent pump 904, (c) shows the lateral position of the
transfer arm 203, (d) shows the relative vertical position of the
probe 202, (e) shows the position of the aliquot syringe 902 and
(f) shows the half-cycle command to relay 747.
The operation of the washing system for cleansing the reaction
tubes after tests have been made is shown in FIG. 13d. This part of
the system is also operated from relay 716 (FIG. 13a). During the
first half-cycle a relay 760 is energised and during the second
half cycle a relay 761 is energized. Relay 760, when energized
applies a signal through a microswitch 762a to a means 763 which
cause a wash pump to discharge into the test tubes. When the
discharge is complete, microswitch 762a actuates and a signal is
then applied to a means 764 which causes the waste pumps to empty
the contents of the reaction tubes. Furthermore, since relay 761 is
de-energized, a signal is applied to a means 765 for lowering the
probes into the test tubes. When relay 760 is de-energized during
the next half cycle and relay 761 is energized, a signal is applied
to a means 766 for lifting the probes and a signal is applied to a
means 767 for causing the waste pumps to discharge and to a means
768 for causing the wash psmp to recharge with wash water. The
processes involved are shown diagrammatically in FIG. 15 where (g)
shows the up-down position of the wash pump, (h) shows the up-down
position of the waste pump and (i) shows the up-down position of
the wash system probes.
A practical arrangement for timing the operations in the apparatus
is shown in more detail in FIG. 20. The timing of operations is
effected by a uni-junction oscillator 800. This oscillator
generates pulses with a periodicity of 1.5 seconds. The
uni-junction device is of the type commercially available under the
designation 2N871. The output of the oscillator is connected to a
decade counter 801 (commercially available as SN7490). Normally the
uni-junction oscillator is prevented from oscillating by the
transistor 802 (of the type commercially designated 2N2222A) which
is held conducting by means of the flip-flop circuit, or bistable
trigger, comprising the two quad 2- input NOR gates 803 and 803a
(of the type SN7402) which have as input signals signals obtained
from the motors in the apparatus and applied to said bistable
trigger through a 2-input NOR gate 804 connected as an inverter.
When the motor 24 is in operation, for example having been started
by pressure on the start button on control panel 13 (FIG. 1)
signals are applied to the terminal 805. The terminal 806 takes the
command from the motor which continues to operate by means of the
microswitch 714. Through the resistor 807 the counter 801 is held
at reset and the transistor 802 is rendered conducting preventing
oscillations. When the control is withdrawn the uni-junction is
allowed to oscillate and this enables the counter 801. After a
count of five, that is after 71/2 seconds, the terminal of counter
801 is connected to a 2- input NOR gate 808 provides a signal which
through a terminal 809 initiates a command signal for the reagent
pumps, the washing devices, and the sample transfer devices. It
will be appreciated that the gate 808 together with the similar
gate 810 constitute a bistable trigger. Both 808 and 810, as are
all the NOR gates in FIG. 20, are of the type SN7402. Every change
of command in the bistable trigger arrangement 808, 810 transfers a
signal from 810 to a decade counter 811 (SN 7490). The counter 811
is connected to a binary to decimal decoder 812 (SN 7442) which
provides signals in turn on the terminals 812a. The outputs 812a
are connected to a selector ssitch to control the relay operating
the motor for the outer belt 2. The purpose of this count is to
count the number of times the reaction belt 5 has moved and, to
allow for the appropriate selection of the number of tests to be
effected, to move the outer belt after two, three, four, five or
six steps of the reaction belt. A signal is applied to another NOR
gate 814 through a terminal 813 from the motor microswitch 722
(FIG. 13b) to indicate that it is turning and this resets the
counter 811. Two NOR gates 815 and 816 constituting a bistable
trigger device are connected so as to be set by the output from
gate 814 and reset by a signal from the lead connecting counter 801
to gate 808. This provides a pulse of 71/2 seconds duration at a
terminal 817 of said trigger which is used to control the
colourimeter head. The signal at terminal 817 is applied through a
transistor 820 (type 2N2222A) and thence to a terminal 819 which
supplies signals to control the coloruimeter. A button is provided
on the control panel 13 (FIG. 1) which when pressed allows the
apparatus to operate without performing any tests, but performing
the washing operations. The effect of pressing the button is to
apply a signal which inhibits the start output 855 for the
colourimeter, whilst the belt 5 continues to move.
The electronic and electrical system which controls the operation
of the colourimeter is shown in block form in FIG. 18, the
waveforms appearing at various points being shown in FIG. 19.
Portion FIG. 18a of the diagram shows the part of the circuit which
controls the timer for the mechanism and FIG. 18b shows the part
which controls the timing for the colourimeter head. The reference
numerals in FIG. 18 are the same as used in FIG. 21 which shows
various parts of the electrical system in greater detail. The start
command to this portion of the circuit is obtained from the main
timer (FIG. 13b) as the output of gate 723 (waveform h in FIG. 14).
This is applied through terminal 855 (waveform b, FIG. 19) to a
bistable trigger 853,854. The output of bistable trigger 853,854 is
applied along a line c (waveform FIG. 19c) through a gate 951, to a
relay 952 which controls the motor 953 for raising and lowering the
colourimeter probes.
An oscillator 850 is provided which produces oscillations having a
period of 1.0 seconds (waveform 19a). The output of bistable
trigger 853, 854 also opens a gate 852 to enable oscillations from
said oscillator 850 to be applied to a counter 851. Said counter
851 provides outputs at respectively 2, 12, 22 and 26 seconds after
commencement of its count. After two seconds, a command is passed
along the conductor d (waveform 19d) through an amplifier 954 to
energize a vacuum solenoid 955. The energizing circuit has a delay
so that the vacuum is applied for approximately nine seconds, the
vacuum being used to draw the contents of the reaction tubes into
the appropriate cuvettes. During the operation of the vacuum
command the sample identification is being read from the marked-up
label on the sample container and being fed to the printer to
produce identification for the proceeding set of colourimetric
results which are relevant to this particular sample container. At
the time 12 seconds after start of the count, the colourimeter head
timing system is initiated by a signal applied along conductor h
(waveform h FIG. 19) to a terminal 862 (FIG. 18b) where said signal
is applied to a gate 861 to set a bistable trigger 859, 860. At a
time 22 seconds after the start of the count, a signal is applied
along a line f (waveform 19f) through an amplifier 956 to a
pressure solenoid 957 which is thus energized in the same way as
was the vacuum solenoid 955 in order to empty the contents of the
cuvettes back into the reaction tubes. At a time 26 seconds after
commencement of the count, a signal is applied from counter 851 to
reset the bistable trigger 853, 854, thus completing the
colourimeter cycle. The lower motion of the motor 953 for the
colourimeter probe is obtained in the same way as the raise motion,
controlled by a signal from terminal 855 applied through a gate 958
to a relay 959. A move right signal for the colourimeter probes is
obtained from the output of relay 730 (FIG. 13b) and applied to the
colourimeter probe horizontal motor 960. A move left signal for
said motor 960 is obtained from microswitch 714'(FIG. 13a) through
relay 961.
Referring to FIG. 18b showing the colourimeter head timing system,
there is provided an oscillator 882 generating oscillations having
a period of 0.6 seconds (waveform j FIG. 19). The output from
bistable trigger 859, 860 is applied to a gate 881 which controls
the supply of said oscillations j to a counter 863, 865.
Said counter 863, 865 has six outputs which generate signals
respectively after 1,2,3,4,5,6 periods of the oscillations of
oscillator 882 on conductors k,l,m,n,o,p (see FIG. 19k,l,m,n,o,p).
These signals are applied to the respective six colourimeter heads
which enable them so as to perform their read functions
sequentially. A seventh output from said counter 863, 865,
appearing after seven periods of said oscillations, is applied to
bistable trigger 859, 860 to reset it. An output from said bistable
trigger 859, 860 is applied along conductor i (waveform i FIG. 19)
to enable operation of the printing mechanism for printing out the
results of the tests.
The colourimeter timing control shown in greater detail in FIG. 21
includes a uni-junction oscillator 850 supplying pulses at one
pulse per second to a decade counter 851 through a 2-input NAND
gate 852. This gate, as are all the gates shown in FIG. 21, is of
the type designated SN7400. The gate 852 is controlled by a
bistable trigger circuit comprising two NAND gates 853 and 854.
Normally the pulses from the oscillator 850 are not supplied to the
counter 851, but when the terminal 855 is energized from the main
timer board, pulses are supplied to the counter. After one second
the counter 851 energises the NAND gate 856 to supply an output to
the terminal 857 which operates a vacuum pressure switch to apply
vacuum to the head and thereby the cuvette probes, which have been
lowered by the pulse applied to terminal 855. The tenth pulse from
the decade counter 851 is applied to a second decade counter 858.
This applies a pulse to the bistable trigger comprising two NAND
gates 859 and 880 through a NAND gate 861 so long as a voltage is
not applied to gate 861 through terminal 862. Terminal 862 is
connected to the wash switch on the control panel 13 (FIG. 1) and
operates to prevent the colourimeter acting. The output of the
bistable trigger 859, 880 enables a NAND gate 881 to allow pulses
from a uni-junction oscillator 882 to reach a decade counter 863
(SN7490) through an inverter 864. This inverter, as are all the
inverters shown in FIG. 21, is of the type designated SN7404. The
decade counter 863 is connected to a binary to decimal decoder 865.
The effect of this is to energise the terminals connected through
respective inverters to the output terminals 866 to 871 for two
seconds each in sequence. The pulses on these terminals are
utilised to control the respective colourimeter heads for the six
tests. On the seventh change, the terminal of the decoder 865
connected to conductor 872 resets the bistable trigger 859, 880 and
stops the supply of pulses from the uni-junction oscillator 882 to
the counter. It also supplies through the bistable trigger a reset
pulse to reset the decade counter 863. After 22 seconds a pulse is
applied to terminal 873 from counter 851 through NAND gate 874. The
pulse on terminal 873 is utilised to apply pressure to discharge
fluid from the cuvettes and to lift the probes clear of the
reaction tubes. After 26 seconds a pulse is applied through the
NAND gate 875 to the bistable trigger 853, 854 to operate gate 852
to remove the supply of pulses to counter 851 from the unijunction
oscillator 850.
The signals provided by the photocells in the colourimeter head are
dealt with as follows. Beer's Law states that the absorbence A is
directly proportional to the concentration C of an absorber, that
is
A = KC where K is a constant.
The output current I of the photocell is directly proportional to
the quantity of light falling on to it and thus to the
transmittance of the sample being tested. By passing this current
through a load resistor R, a voltage V is obtained represented
by
V = I R = KT where K is a constant.
Since from Beer's Law we have A = -log T, then T = 10.sup..sup.-A.
Thus V has an inverse logarithmic relationship to the concentration
of reaction product. This is converted to a linear reading of
concentrations as follows: Referring to FIG. 22a,V.sub.O is at a
maximum when the cuvette is filled with reagent only, for example
when distilled water has been substituted for a sample. In this
case, the voltage produced by the photocell 1001 across the load
resistor 1002 is V.sub.O. By connecting a centre-zero meter 1003
between the output of said photocell 1001 and the wiper of a
potentiometer 1004 connected between ground and a stable reference
voltage V.sub.R the wiper may be set to provide a voltage V.sub.O.
If a capacitor 1005 is now connected to the wiper of the
potentiometer 1004 through a switch 1006 (see FIG. 22b) the
capacitor 1005 will charge to a potential V.sub.O. If the switch
1006 is now changed over so as to allow the capacitor 1005 to
discharge through a resistor 1007 of value R.sub.C, the voltage of
said capacitor 1005 will fall in a logarithmic decay curve as shown
in FIG. 23. With a sample in the cuvette, the output from the
photocell will be V, always less than V.sub.O. If this is compared
with the decaying voltage across the capacitor 1005 in a comparison
circuit 1008 (FIG. 22c) an output can be obtained from said
comparator constituting a pulse P (FIG. 23). The duration of this
pulse will be directly proportional to the concentration of
reaction product in the cuvette. The pulse duration is measured by
a four-decade digital timer 1009 and its output can be displayed
and printed.
* * * * *